Please click on one of the subjects below for more more information about that subject. General Information Does Aluminum Cause Alzheimer's Disease? Does A Virus Cause Alzheimer's Disease? Do Bacteria Cause Alzheimer's Disease? Scientific References GENERAL INFORMATION The exact cause of alzheimer's disease is still uncertain. Genetic mutations, for example, clearly do cause the disease. For example, mutations in the presenilin 1 gene cause more than half of all cases of early-onset alzheimer's disease. Most researchers today believe the immediate cause of alzheimer's disease is the abnormal build-up in the brain of a substance called amyloid beta peptide [abbreviated AB]. AB is formed by abnormal cleavage of a parent substance called amyloid precursor protein [abbreviated APP]. APP , which protects brain cells from injury, is a protein made up of up to 771 amino acids. AB, which is only 40 to 43 amino acids long, is formed when two enzymes, beta secretase and gamma secretase , cleave APP abnormally, thus releasing AB. Normal cleavage of APP by alpha secretase enzymes does not form AB. Genetic mutations that result in early-onset alzheimer's disease increase the amount of AB in the brain. Animals have been created in the lab,and these mice and rats have had alzheimer genes inserted in their DNA. Mice or rats, with human alzheimer genes inserted in their DNA, are known as transgenic animals. Transgenic animals show build up of AB in their brains just like alzheimer patients do. Transgenic animals also show decreased learning and memory, like alzheimer patients. Elan Pharmaceuticals recently developed a potential vaccine for alzheimer's disease. The company has found that transgenic mice, which normally have high AB levels in their brains as they age, show less build-up of AB when given the new vaccine. In addition, the transgenic mice show better memory and learning capacity than transgenic mice not given the vaccine. Work with such transgenic animals seems to show that AB is the immediate cause of alzheimer's disease. Drug companies are looking for drugs that can reduce levels of AB in the brain, blood, and cerebrospinal fluid. An exciting new development is a recent study which reports that people who take cholesterol-lowering drugs seem to have a lower incidence of alzheimer's disease. Researchers now know that cholesterol-lowering drugs may actually stop the production of AB. For example, one commonly-used cholesterol-lowering drug, simvastatin, directly reduces the production of AB in cultured brain cells that have been engineered to overproduce AB. This new work suggests that cholesterol may be involved in AB production. Some researchers feel that envvironmental factors may be important causes of alzheimer's disease. For example, in the early 1980's, alzheimer researchers were excited about the possibility of aluminum as the cause of alzheimer's disease. Aluminum may play an intriguing role in alzheimer's disease, as we shall see in the next section. DOES ALUMINUM CAUSE ALZHEIMER'S DISEASE ? In the early 1980's some researchers found aluminum in the cores of senile plaques. The fact that aluminum was found close to AB deposits in senile plaques suggested that it might be a cause of alzheimer's disease. Aluminum was further suggested as a cause of dementia because it had been noted that dialysis patients, who sometimes develop dementia, had high aluminum levels in their blood. Workers began to look for aluminum in the brains of alzheimer patients. Some studies,indeed, did find high aluminum levels in the brains of patients. However, just as many studies failed to find aluminum in the brains of patients. An additional complication was that other metals, such as silica, iron, and zinc were found in senile plaques, along with aluminum. Such results cast doubt on aluminum as the cause of alzheimer's disease. Other studies cast doubt, too. One study showed that heavy users of aluminum-containing antacids did not show an increased incidence of alzheimer's disease [1]. A study of workers in the aluminum industry also failed to show a higher incidence of alzheimer's disease [2]. Some new studies have revived aluminum as a possible cause of alzheimer's disease. Aluminum, in cultured tissue, can cause AB to aggregate and clump together[3]. Other metals, such as iron and zinc, can also cause AB to clump together in insoluble deposits. One study showed that aluminum was able to induce more AB aggregation than iron or zinc [4]. Several recent studies have also found aluminum to be higher in the blood of alzheimer patients[5,6]. Two studies have shown that when alzheimer patients and normal elderly are given a drink containing aluminum citrate, alzheimer patients consistently absorb more aluminum in their gastrointestinal tract than do normal elderly [7,8]. The fact that alzheimer patients may absorb more aluminum from what they drink has added significance when you consider some other evidence. Seven studies I have reviewed show that high aluminum in drinking water increases the risk for alzheimer's [9,10,11,12,13,14,15]. Only one study was negative [16]. A study done last year reports that alzheimer risk is doubled when aluminum content in drinking water is greater than 0.1 milligram per liter. The study also finds that dissolved silica in the water actually decreases risk . Clearly, aluminum increases alzheimer risk, but exactly how remains unclear. DOES A VIRUS CAUSE ALZHEIMER'S DISEASE ? Some researchers speculate that a "slow" virus could be the cause of alzheimer's disease. A slow virus can lie dormant in the body for years. When conditions are favorable, the virus becomes active. Herpes simplex virus 1 [HSV-1] is the name given to the virus that causes cold sores on lips. HSV-1 is extremely common and lies dormant in virtually everyone. Sunlight or cold infections can activate the virus. The HSV-1 virus is a risk factor for alzheimer's disease. People with an apolipoprotein E4 gene are at increased risk for alzheimer's disease late in life. People who have both high HSV-1 viral exposure and an E4 gene have a 3-fold higher risk for alzheimer's disease than people with only the E4 gene or high HSV-1 expression [17,18]. The HSV-1 virus is an important risk factor for alzheimer's disease. To date, no other virus has been implicated as a risk factor for alzheimer's disease. DO BACTERIA CAUSE ALZHEIMER'S DISEASE ? Bacteria can cause brain infection and dementia. For example, Treponema pallidum,the spirochete that causes syphilis, attacks the brain and causes a form of dementia in the late stage of syphilis. Bacteria have been found in alzheimer brains. One study found filamentous Actinomycetes bacteria increased 4-fold in alzheimer brains,but not non-demented elderly[19]. Recently, a team at Hahnemann Medical University in Philadelphia, Pennsylvania, found evidence that only alzheimer brains were infected by a common bacterium called Chlamydia pneumoniae [20]. A follow-up study by another group did not detect any evidence of Chlamydia pneumoniae in the brains of alzheimer patients [21], so it seems this matter is still unresolved at this time. SCIENTIFIC REFERENCES 1. Colin-Jones,D.,et.al.,Alzheimer's disease in antacid users. Lancet,1989,1:1453 2. Salib,E.et.al.,A case control study of alzheimer's disease and aluminum occupation. Br J Psychiatry,1996, 168:244-249 3. Exley,C.,et.al.,Aluminum,beta amyloid and non-enzymatic glycosylation. FEBS Letters,1995,364: 182-184. 4. Shearman,M.,et.al.,The relative importance of metal ions for beta amyloid toxicity: a reply. Biochem J,1995,314:709-711. 5. Zapatero,M.D.,et.al.,Serum aluminum levels in alzheimer's disease and other senile dementias. Biol Trace Elem Res,1995,47:235-240. 6. Corrigan,F.M.,et.al.,Transferrin,cholesterol, and aluminum in alzheimer's disease. Clin Chim Acta, 1992,211:121-123. 7. Taylor,G.A.,et.al.,Gastrointestinal absorption of aluminum in alzheimer's disease: response to aluminum citrate. Age Ageing,1992,21:81-90. 8. Moore,P.B.,et.al.,Gastrointestinal absorption of aluminum is increased in Down's syndrome. Biol Psychiatry, 1997,41:488-492. 9. McLachlan,D.R.,et.al.,Risk for neuropathologically confirmed alzheimer's disease and residual aluminum in municipal drinking water employing weighted residential histories. Neurology ,1996, 46:401-405. 10. Giordano,R.,et.al.,Some aspects related to the presence of aluminum in waters.Ann 1st Super Sanita,1993,29:305-311. 11. Forbes,W.F.,et.al.,Further thoughts on the aluminum- alzheimer's disease link. J Epidemiol Commun Health,1996,50:401-403. 12. Jacqmin-Gadda,H.,et.al.,Silica and aluminum in drinking water and cognitive impairment in the elderly. Epidemiology, 1996,7:281-285. 13. Martyn,C.N.,et.al.,Geographical relation between alzheimer's disease and aluminum in drinking water. Lancet,1989,1:59-62. 14. Still,C.N.,et.al.,On the incidence of primary degenerative dementias: water fluoride content in South Carolina. Neurotoxicology,1980,4: 125-131. 15. Flaten,J.P.,et.al.,Geographic association between aluminum in drinking water and registered death rates with dementia(including alzheimer's disease) in Norway. Environ Geochem Health,1990,12:152-167. 16. Forster,D.P.,et.al.,Risk factors in clinically diagnosed presenile dementia of the alzheimer type: a case control study in Northern England. J Epidemiol Commun Health,1995,49:253-258. 17. Lin,W.R.,et.al.,Neurotropic viruses and alzheimer disease.Interaction of herpes simplex type 1 virus and apolipoprotein E in the etiology of the disease. Mol Chem Neuropathol,1996,28:135-141. 18. Lin,W.W.,et.al.,Alzheimer's disease,herpes simple virus type 1, cold sores,and apolipoprotein E4. Biochem Soc Trans,1995,23:5945 19. Howard,J.,et.al.,Fibronectin staining detects micro-organisms in aged and alzheimer's disease brain. Neuroreport,1992,3:615-618. 20. Balin,B.J.,et.al.,Identification and localization of Chlamydia pneumoniae in the alzheimer's brain. Med Microbiol Immunol,1998,187:23-42. 21. Ring,R.H.,et.al.,Failure to detect Chlamydia pneumoniae in the late-onset alzheimer brain. J Clin Microbiol,2000,38:2591-2594.
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